Phenylephrine

MECHANISM OF ACTION

Phenylephrine is a direct sympathomimetic amine that acts as an alpha-1 adrenergic agonist. The drug's molecular structure is similar to epinephrine and ephedrine, and it has strong vasoconstrictive properties when delivered intravenously or directly to mucosal membranes. The total effect of IV phenylephrine on cardiac output and end-organ perfusion is likely to be more complicated and vary depending on the dosage type (bolus or infusion), volume status, baseline heart rate, autonomic tone, and underlying cardiac diseases. These differences are due to the degree of vasoconstriction, which may cause a brief rise in preload, arterial constriction, which leads to increased systemic vascular resistance and afterload, and reflex bradycardia. These variables combined have a mixed influence on cardiac output, which varies depending on the patient group. Phenylephrine binds to alpha-1 receptors, which innervate the iris dilator muscle, causing smooth muscle contraction and pupil dilation upon ophthalmic administration. This dilatation can help in fundoscopic examinations, enhance exposure during some procedures, and facilitate the treatment of numerous medical disorders.

PHARMACOKINETICS

Absorption

Phenylephrine's absorption profile varies according to the method of administration. The medication's ocular administration enables fast absorption through the conjunctiva and cornea, resulting in a beginning of effect in minutes. IV treatment provides quick and full bioavailability, enabling rapid systemic dispersion. Although rectal administration of the medicine is slower than nasal and IV administration, it results in mucosal absorption, with peak concentration usually reached in 30 to 60 minutes. Nasal administration allows for fast mucosal absorption, resulting in peak plasma concentrations in 15 to 30 minutes.

Distribution

Because of its lipophilic nature, phenylephrine readily enters vascular-rich tissues after absorption, allowing it to exert central and peripheral effects. Ophthalmic formulations limit distribution to ocular compartments, causing pupil dilatation without having a large systemic influence. The steady-state volume of distribution of 340 L is more than the body's entire volume, suggesting a significant volume of distribution.

Metabolism

The principal metabolic routes for phenylephrine are sulphate conjugation, largely occurring in the intestinal wall, and oxidative deamination mediated by monoamine oxidase (MAO)-A and MAO-B enzymes. Glucuronidation also provides an alternative metabolic pathway for phenylephrine.

Elimination

The primary method of phenylephrine elimination is renal excretion; regardless of the method of administration—nasal, ocular, or rectal—the majority of the drug is eliminated unchanged in urine. Because of its short half-life of 2.5 to 3 hours, phenylephrine requires frequent dose intervals, especially when administered intravenously, to maintain therapeutic efficacy.

PHARMACODYNAMICS

Phenylephrine is an alpha-1 adrenergic agonist that increases blood pressure, dilates pupils, and induces local vasoconstriction. Phenylephrine ophthalmic preparations have a 3–8 hour action time, but intravenous solutions have a 5-minute effective half-life and a 2.5-hour elimination half-life. Patients who use phenylephrine ophthalmic formulations should be informed about the risk of tachycardia, hypertension, and rebound miosis. Patients receiving an intravenous formulation should be advised of the possibility of bradycardia, allergic reactions, extravasation resulting in necrosis or tissue sloughing, and the use of oxytocic medications concurrently.

DOSAGE AND ADMINISTRATION

The most popular methods of administering phenylephrine include topical, IV, intranasal, ophthalmic, and rectal. Oral formulations should be avoided because they are ineffective.

Phenylephrine, albeit less common, has been used as an adjuvant to peripheral nerve blockade in the epidural space, intracavernally, intramuscularly, and subcutaneously. When administering phenylephrine intravenously, the typical dose range is 50 to 100 mcg in aliquot. Because of its rapid start of action (1 to 3 minutes) and relatively short duration of impact (5 to 20 minutes), the medication commonly needs repeated administration.

Phenylephrine ophthalmic solutions come in a variety of concentrations and ingredients that can be customised to achieve specific results. Medical practitioners frequently employ these concentrations, which come in strengths of 1%, 2.5%, and 10%. The 1% formulations are typically used with 0.2% cyclopentolate for dilated fundus and cycloplegic exams in neonates under 3 months old. The 2.5% formulations are the ideal choice for dilated fundus examinations in adults and children over the age of three months, as well as for diagnosing episcleritis. Although the 10% formulation is less commonly utilised due to concerns about systemic absorption, it can be used for dilated inspections and exposure during surgical procedures.

CONTRAINDICATIONS

Phenylephrine has no specific contraindications, with the exception of allergy to the medicine or its components. In sensitive people, sodium metabisulfite in IV phenylephrine can cause allergic reactions such as anaphylaxis symptoms or less severe asthmatic episodes. The actual prevalence of sulfite sensitivity is unknown, however, it is likely minimal.

DRUG INTERACTIONS

The drugs listed below efficiently enhance the pressor action of phenylephrine.
Prednisone: Prednisone and other steroids sensitise the vasculature to catecholamines like phenylephrine, which increases their vasoconstrictive impact.

Amitriptyline: Amitriptyline is a tricyclic antidepressant that decreases the reuptake of endogenous norepinephrine, prolonging its action and amplifying the effects of phenylephrine.

Alpha-1 adrenergic antagonists: These antagonists block phenylephrine's vasoconstrictive effects by directly inhibiting alpha-1 receptors on smooth muscle.

SIDE EFFECTS

The common side effects of phenylephrine include

• Dizziness
• nervousness
• chest pain
• blurred vision
• sweating
• nausea or vomiting
• tiredness
• irregular heartbeat

TOXICITY

Currently, there is no recognised antidote to IV phenylephrine. Hypertension caused by excessive dosage or an exaggerated reaction is usually temporary, owing to the brief duration of action. To treat hypertension or symptomatic reflex bradycardia, stop providing phenylephrine and instead use chronotropic drugs or vasodilators as needed. The therapy for tissue extravasation caused by peripherally given phenylephrine is essentially supportive, including fluid aspiration, warmth, and elevation.